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Cell biologist awarded top science prize

Medicine@Yale, 2010 - July Aug


2010 Kavli Prize in Neuroscience honors researcher’s deciphering of membranes’ role in shuttling proteins within and between cells

On June 3, James E. Rothman, Ph.D., the Fergus F. Wallace Professor of Biomedical Sciences and chair of the medical school’s Department of Cell Biology, was named a recipient of the 2010 Kavli Prize in Neuroscience. The biennial $1 million award, which has become one of the most prestigious in science, was established in 2008 by a partnership of the Norwegian Association of Science and Letters, the U.S.-based Kavli Foundation, and the Norwegian Ministry of Education and Research.

Rothman is one of the world’s foremost experts on membrane trafficking, the means by which proteins and other materials are transported within and between cells. The Kavli Prize highlights his contributions to the understanding of exocytosis, a form of trafficking in which spherical sacs called vesicles fuse with cell membranes to deliver their contents outside the cell.

This process is ubiquitous in biology—it is essential to cell division and insulin secretion, for example—but exocytosis plays a particularly crucial role in the nervous system. In neurons, vesicles carrying neurotransmitters fuse with cell membranes at synapses, emptying their cargo to pass on the chemical messages that govern movement, perception, cognition, memory, and mood. For three decades, Rothman has performed elegant, focused biochemical and cell biology experiments that have revealed the molecular machinery of membrane trafficking in fine detail. Much of this work was done using a “cell-free” approach, in which Rothman sidestepped the complexities of working with complete cells by isolating the intracellular components crucial to membrane trafficking. This strategy allowed him to propose that complexes of membrane-associated proteins known as SNAREs are required for vesicles to fuse with membranes.

Rothman shares the Kavli Prize with Thomas Südhof, Ph.D., of the Stanford School of Medicine, and Richard H. Scheller, Ph.D., formerly at Stanford and now Executive Vice President of Genentech.

While at the University of Texas Southwestern Medical Center, Südhof discovered synaptotagmin, a protein in vesicle membranes that senses intracellular calcium levels. When a neuron is stimulated, calcium binds to synaptotagmin, which prompts the vesicle to release its contents by interacting with SNARE complexes and fusing with the cell membrane. Structural, genetic, and cell biology studies in Scheller’s lab have mapped out the interactions of synaptotagmin and SNAREs during exocytosis with great precision.

In addition to the neuroscience prize, Kavli Prizes in astrophysics and in nanoscience are also awarded every two years by the NASL. Rothman’s is the second consecutive Kavli Prize in Neuroscience won by a School of Medicine researcher. In 2008, Pasko Rakic, Ph.D., Dorys McConnell Duberg Professor of Neurobiology, shared the prize for his research on the cerebral cortex.

In 2004, the Kavli Foundation, led by Norwegian-born entrepreneur and philanthropist Fred Kavli, established the Kavli Institute for Neuroscience at Yale. Directed by Rakic, it is one of only four such institutes nationwide.